The invention relates to “active implantable medical devices” as defined by Directive 90/385/EEC of 20 Jun. 1990 of the Council of the European Communities, and more precisely implants that continuously monitor cardiac rhythm and deliver, if necessary, electrical stimulation, resynchronization and/or defibrillation pulses to the heart, in case of a rhythm disorder detected by the device.
Anti-bradycardia stimulation involves monitoring electrical potentials of depolarization of the myocardium, and controlled delivery of pulses to the atrium and/or to the ventricle. In the case of a cardiac resynchronization therapy (CRT), stimulation is applied jointly to both ventricles.
An embodiment is described more precisely in the context of an implant that continuously monitors the cardiac rhythm and delivers electrical pulses to the heart, if necessary, to stimulate the left and right ventricles jointly and permanently to resynchronize them. The technique is called CRT or bi-ventricular pacing (BVP).
This particular case does not, however, limit the disclosure, which by a number of its aspects, is also applicable to “single chamber” devices wherein detection/stimulation only occurs in the right ventricle, or “dual chamber” devices wherein detection/stimulation occurs only in the right ventricle and in the right atrium.
A CRT pacemaker is disclosed, for example, in EP 1108446 A1 (Sorin CRM), which describes a device for applying, between the respective moments of stimulation of the left and right ventricles, a variable interventricular delay (DVV or VVD), adjusted to resynchronize the contraction of the ventricles with fine optimization of the patient's hemodynamic status. The VVD can be zero, positive (the left ventricle is stimulated after the right ventricle) or negative (the right ventricle is stimulated after the left ventricle).
This CRT device further includes a classical dual chamber operating mode pacemaker, wherein the device monitors the ventricular activity after a spontaneous (P-wave) or stimulated (pulse A) atrial event and triggers a stimulation of the right ventricle (V pulse) if no ventricular spontaneous activity (R wave) has been detected at the end of a said atrioventricular delay (AVD).
The present disclosure relates more particularly to long term monitoring of the patient' cardiac status and how this status changes, in particular to diagnose the occurrence of the phenomenon referred to as “cardiac remodeling in the patient.” Cardiac remodeling can be defined as all the changes of the heart generated in response to a disease, which is generally associated with a bad prognosis.
Indeed, clinical changes being possibly asymptomatic, it is common that the patient unconsciously adapts its activity to his/her clinical status. At the first sign of heart failure crises appearing due to stress, the patient may reduce his/her activity to avoid the occurrence of such crises. The symptoms no longer appear because the patient changed his/her behavior to avoid them, but the disease continues to progress.
Remodeling occurs in the long run by increasing the volume of the left ventricle, with deterioration in the ejection fraction and of the intraventricular pressure regime due to the decrease of contractility and/or the excessive pressure downstream and, ultimately, by a decrease in cardiac output resulting in serious consequences for the body when heart failure progresses. It is only when the heart failure hinders the patient even at rest when he/she will consult a physician or, in extreme cases, be admitted to emergency.
In summary, due to self-adjustment, the lack of symptoms experienced by the patient introduces a significant delay between the onset of clinical changes and diagnosis of these changes, which is often too late.
By stimulating both ventricles in a controlled method, the CRT therapy optimizes the contraction/relaxation cycle with a direct benefit of facilitating the heart activity, which can help stabilize the remodeling phenomenon and even counter it (“reverse remodeling”), with a better prognosis for the patient.
According to exemplary embodiments, the present disclosure provides diagnostic methods incorporated into a pacemaker (CRT or other) that would provide regular monitoring (e.g., daily) of the patient's condition, especially to monitor the evolution of a cardiac remodeling (deleterious) or of a reverse remodeling (beneficial). This monitoring should be early enough to allow rapidly taking appropriate actions (such as a change in a setting of therapy or switching of this therapy to another therapy if it is not effective), thus avoiding the unexpected occurrence of a crisis in the short and medium term. In the case of a detected sudden worsening, it may be possible to alert the doctor immediately, for example by remote transmission of a message to a remote monitoring site.
A reference technique for evaluating long-term changes in the patient's heart condition, and therefore for determining the effectiveness of therapy and possibly adjusting the stimulation parameters, is echocardiography with the measurement of the ventricular volume and estimate of the characteristic delays of the systole, in particular estimation of the opening time of the aortic valve. This procedure, however, must be implemented in hospitals and by qualified personnel. The procedure is long and expensive and cannot be applied as often as would be useful or necessary without interfering with the patient's daily life.
Automatic analysis techniques from the implantable device have also been proposed, for example, by US 2011/0152660 A1, wherein the worsening and improving of the patient are evaluated from the evolution of the interventricular conduction delay considered alone or in combination with the evaluation of the patient's activity and/or the presence of pulmonary edema.
This method is however very sensitive to the position of the leads, as well as how the heart remodels. Therefore, in some cases the analysis may not provide the desired information, in particular if no significant change in the conduction delay is observed along the measurement axis, while according to another axis a much larger variation could have been observed.
US 2007/0239037 A1 describes another technique, based on the measurement (by ultrasound) of the interventricular conduction delay prior to implantation of the device. It aims at predicting the response of a patient to a CRT therapy. The greater the initial interventricular conduction delay is, the more likely it is that a significant remodeling is present. This is, however, not a diagnostic tool to assess the long term evolution of a patient's condition, after implantation of the device.
US 2007/0043394 A1 describes a technique for diagnosis of heart failure by detecting a variation of the intracardiac impedance at a constant heart rate. The evolution of this parameter in the long term can be used to determine whether the heart remodels. The measurement of the intracardiac impedance is not however a stable parameter in the long term (several weeks or months), which renders the operation difficult for diagnostic purposes with a sufficient degree of certainty.
US 2009/0270747 A1 (U.S. Pat. No. 7,996,070 B2) operates by analyzing the electrocardiogram (ECG) collected by a subcutaneous implant. Changes in the morphology of the signals are detected and evaluated, distinguishing those related to the cardiac condition of the patient from those related to changes in position of the latter. But these teachings are not transferable to a cardiac implant collecting endocardial electrogram signals (EGM), which have a quite different morphology.